Is COLQ p.Arg341Ser (c.1023A>T) pathogenic?

COLQ p.Arg341Ser (c.1023A>T) is classified Uncertain significance in COLQ (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-31). AlphaMissense: ambiguous (0.5263); Absent from gnomAD v4.1; Associated with congenital myasthenic syndrome 5.

What condition is associated with COLQ p.Arg341Ser (c.1023A>T)?

COLQ p.Arg341Ser (c.1023A>T) is associated with congenital myasthenic syndrome 5 (ClinVar).

How common is COLQ p.Arg341Ser (c.1023A>T) in the general population?

COLQ p.Arg341Ser (c.1023A>T) is absent from gnomAD v4.1 (gnomAD).

How is Congenital myasthenic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about COLQ p.Arg341Ser (c.1023A>T)?

AlphaMissense predicts ambiguous (score 0.5263) — an in-silico prediction, not a clinical call.

COLQ p.Arg341Ser

c.1023A>T · VCV4078405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5263 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital myasthenic syndrome 5

Computational evidence

Protein change
AlphaMissense	0.5263	ambiguous
REVEL	0.435	indeterminate
SaProt	LLR -8.31	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.003, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 70 kb · p 0.34 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COLQ
Protein: p.Arg341Ser
Coding: c.1023A>T
MANE Select: NM_005677
Type: single nucleotide variant
Location: chr3:15456511 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 55.25 · 2 PDB
Residue 341: a UniProt-annotated variant site (in cms5; pathogenic); a UniProt-annotated variant site (in cms5; pathogenic; impaired anchoring of asymmetric ache to the synaptic basal membrane)

Full COLQ gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myasthenic syndrome 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital myasthenic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

COLQ p.Arg341Gly Uncertain significance ★ ⚠ same residue
COLQ c.1195+1G>A Pathogenic ★★ same condition
COLQ c.1298+3A>G Pathogenic ★★ same condition
COLQ c.219+1G>C Pathogenic ★★ same condition
COLQ c.220-1G>A Pathogenic/Likely pathogenic ★★ same condition
COLQ c.393+1G>A Pathogenic ★★ same condition
COLQ c.529-2A>G Pathogenic/Likely pathogenic ★★ same condition
COLQ c.555+1G>A Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/colq-p-arg341ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown